The immune and oxygen system is a vital part of the body's functions and defense mechanism against illness and disease for animals and humans. Really any living thing, including plants and microorganisms utilize an internal system for combating stress and adversity. This system's ability to respond to disease, supply energy to tissues, detoxify the body against pollution and drugs, conduct neuromuscular signaling, etc., varies from individual to individual and from day to day within the same individual. This system will be briefly referred to herein as “the immune system.”
For example, a patient suffering from Hepatitis C, cancer, other disease, or even a physical or psychological stress, may have a taxed immune system. Certain immunotherapy drugs designed to boost or modulate the immune system, such as Interferon for Hepatitis C, or cytokines and/or activated T-cells for cancer, help the individual's immune system to fight a given disease. Interferon, for example, can help an individual fight Hepatitis C. However, not all individuals respond to the same extent to immunotherapy.
The distinction among responses to immunotherapy was shown in a clinical study for evaluating Hepatitis C patients on Interferon treatment, as approved by the Institutional Review Board of the University of Medicine and Dentistry of New Jersey. In summary of this study, the existence of non-responders to Interferon treatment of Hepatitis C patients is well known. A review is provided by Dr. William M. Lee at the University of Texas Southwestern Medical School. Dr. Lee and colleagues at nine other institutions worked on the HALT-C study from 2002-2007. This study points out that there are 50-60% of non-responders to Interferon plus ribavirin treatment. These non-responders are furthermore non-responsive to long-term Interferon maintenance strategies in the sense that there is no significant difference in the rate of progression of liver disease between non-responders on Interferon and non-responders not on Interferon maintenance. The question that arises from this work is: Why is there a difference between responders and non-responders?
Hinshaw, Sofer, and coworkers (Am. J. Physiol Heart Cir. Phys: H742-750 (1980)) found when studying an extracorporeal blood recirculation system in canine endotoxic shock models, that the shear stress generated by the extracorporeal pump circulation system led to autoanticoagulation. That is, stressed blood would not clot, in the absence of external anticoagulants such as heparin, even in a vigorously agitated blood circulation system. They further isolated from stressed blood, HLF, a heparin-like factor (please see reference to bNOS below), which was shown to prevent clotting. Hinshaw and coworkers (Circ. Shock 1979; 6(3)261-9) also noted that such stressed blood in canines led to a ‘cure’ in the dogs, the autoanticoagulated dogs, were resistant to shock when injected with bacterial endotoxin.
The inventor here, Sofer, pursued this problem as a New Jersey State Sponsored Research Professor of Biotechnology, and discovered MOPs, or molecular oxygen peaks (not radical oxygen species) emanating from blood that were generated from stressed blood (Comparative Haematology International (1999) 9:68-71). Other published works based on thousands of runs by Sofer's NJIT Biotechnology group reinforce the presence of oxygen peaks generated by many other types of stress: chemical, thermal, pH, etc. The questions that arise here are: Where does the oxygen from the MOPs come from, in view of the fact that the MOPs are generated from blood at zero oxygen concentration, where the hemoglobin equilibrium oxygen content is zero? Why does stress release this oxygen? Why does stress strengthen the immune system against bacterial endotoxin attack? These questions were not clarified by these researchers.
While Sofer's group acknowledged the possibility that the probe they used for oxygen measurements may also read Nitric Oxide or H2S or other compounds, they did not consider the combined action of oxygen with these compounds, nor did they postulate the existence of NO—or other—reservoirs.
In a thorough review of the literature of NO, Pieper (Hypertension. 1998; 31:1047-1060.) Galen M. Pieper, Review of Alterations in Endothelial Nitric Oxide Production in Diabetes) does not teach that oxygen or NO or others are present in reservoirs, nor does he propose their combined actions. Furthermore, this review fails to consider the rates of change of the concentrations of these materials as a function of time, i.e., the slopes of curves relating to rates of reaction. He points out the inconclusiveness of NO science with respect to many of the major diseases.
Maltepe and Sougstad (Maltepe, Emin; Saugstad, Ola Didrik, Oxygen in Health and Disease: Regulation of Oxygen Homeostasis-Clinical Implications Pediatric Research: March 2009—Volume 65—Issue 3—pp 261-268) offer a detailed review of the role of oxygen in health and disease. They do not consider oxygen or NO or other reservoirs, or their combined actions. Any of the foregoing references cited in the background are incorporated in their entirety herein by reference.
Thus there is a need for a way to assess or quantify the ability of an individual's immune system to ward off disease and to respond to immune system-boosting drugs such as Interferon.